Combined brain and peripheral nerve stimulation to enhance beneficial effects of

结合大脑和周围神经刺激，增强有益效果

• 批准号: 8730241
• 负责人: ADRIANA B CONFORTO
• 金额: $ 11.33万
• 依托单位: FUNDACAO FACULDADE DE MEDICINA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8730241
• 关键词: Activities of Daily Living; Address; Adult; Affect; Animals; Applications Grants; Area; Biomedical Engineering; Brain; Brazil; Cerebrovascular Disorders; Chronic Phase; Clinic; Clinical; Collaborations; Country; Coupled; Crossover Design; Data; Devices; Electric Stimulation; Equipment; Funding; Grant; Hand; Hand functions; Healthcare; Hospitals; Human; Income; Independent Living; Institution; Intervention; Investigation; Laboratories; Link; Motor; Movement; Muscle; National Institute of Neurological Disorders and Stroke; Neurologic; Neurons; Operative Surgical Procedures; Outcome; Pain; Painless; Paralysed; Patients; Performance; Peripheral; Peripheral Nerve Stimulation; Peripheral Nerves; Physiology; Placebo Effect; Placebos; Protocols documentation; Quality of life; Rehabilitation therapy; Research; Research Infrastructure; Research Personnel; Sensory; Staging; Stroke; Techniques; Testing; Therapeutic; Time; Training; Translational Research; United States National Institutes of Health; Universities; Upper Extremity; Work; design; disability; evidence base; experience; global health; improved; innovation; motor function improvement; motor impairment; multidisciplinary; neuroregulation; neurosurgery; novel; novel strategies; professor; restoration; somatosensory; stroke rehabilitation; tool; training aid

DESCRIPTION (provided by applicant): Worldwide, every other second someone suffers a stroke, the #1 cause of disability in western countries. The catastrophic burden of stroke and the scarcity of evidence-based rehabilitation interventions to decrease disability from stroke represent a major challenge to global health care. There is a gap between studies in animals demonstrating "rewiring" of neuronal circuits and availability of neurorehabilitative strategies to restore independent living in the clinical domain. Basic infrastructure to implement research in stroke rehabilitation has been developed at the Neurostimulation Laboratory at Hospital das Clmnicas/ Sao Paulo University/ Fundagao Faculdade de Medicina, Brazil, in great part due to a previous successful R21 grant funded by NIH. A strong partnership was developed between the Neurostimulation Laboratory and the Human Cortical Physiology and Stroke Rehabilitation Section at NINDS. In the R21 grant, peripheral sensory stimulation (PSS) was applied to enhance effects of training in patients in with stroke. In PSS, electrical currents are delivered to peripheral nerves, in the absence of pain. Increase in sensory input by PSS enhances excitability of brain motor areas and can improve hand motor performance, as demonstrated by results from our R-21 grant and from other studies. Another painless emerging technique to enhance motor function is transcranial direct current stimulation (tDCS) that enhances brain excitability non-invasively. Most neuromodulation research to improve motor function in stroke has focused on patients with mild hand motor impairment. This grant proposal will build on results of the R-21, by using a novel approach to treat patients with moderate to severe hand weakness in the chronic phase after stroke, to whom there are virtually no universally accepted options to decrease hand disability. In these patients, electrical currents delivered to muscles in the form of functional electrical stimulation (FES) can assist movement performance and motor training. We will combine FES, PSS and tDCS in an innovative strategy. The first aim of this grant is to compare effects of a single session of FES in close association with either tDCS alone, PSS alone, tDCS + PNS or sham tDCS + sham PSS, on motor impairment of patients with moderate to severe upper limb weakness in the chronic phase after stroke. The second aim is to compare the effects of several sessions of the most powerful neuromodulation intervention according to results of Aim 1, and effects of placebo (sham PSS/tDCS) combined with FES + task-specific training, on the ability to perform activities of daily living. In Aim 2, the interventions will be administered over six weeks to two groups of adult stroke patients with moderate to severe hand weakness. The proposed paradigm represents a step forward to break barriers in translational research by means of a multidisciplinary link. The P.I., Dr. Conforto, chief of the Neurostimulatation Laboratory in Brazil, the middle-income country (MIC) institution, will collaborate with researchers from high-income country (HIC) institutions: Dr. Leonardo Cohen, an eminent researcher that leads the Human Cortical Physiology and Stroke Rehabilitation Section at Intramural NINDS; Dr. P. Hunter Peckham, a distinguished researcher and pioneer on FES, who is Professor of Biomedical Engineering at the Case Western Reserve University; Dr. Andre Machado, Director of the Center for Neurological Restoration and Assistant Professor of Surgery in the Neurosurgery Department at the Cleveland Clinic, who has extensive experience in neuromodulation protocols. The collaboration between MIC and HIC institutions will set the stage for advancing research on non-invasive cortical neuromodulation and biomedical engineering, needed to ripen strategies for stroke rehabilitation. Equipment and facilities are available at the MIC institution that will provide full support to this proposal.

描述（由申请人提供）：全球，每一秒钟都遭受中风，这是西方国家残疾的第一名。中风的灾难性负担和基于证据的康复干预措施减少中风的残疾，这是全球医疗保健的主要挑战。在动物中的研究之间存在差距，表明神经元回路的“重新布线”与神经居住策略的可用性，以恢复生活在临床领域中的独立生活。在巴西的Das Clmnicas/ Sao Paulo University/ Fundagao Faculdade de Medicina的医院的神经刺激实验室已经开发了实施中风康复研究的基本基础设施，这在很大程度上是由于先前的成功R21赠款。 Ninds的神经刺激实验室与人类皮质生理学和中风康复部门之间建立了牢固的伙伴关系。在R21赠款中，应用周围感觉刺激（PSS）来增强中风患者的训练影响。在PSS中，在没有疼痛的情况下，将电流传递到外周神经。如我们的R-21赠款和其他研究的结果所证明，PSS的感觉输入增加可增强脑运动区域的兴奋性，并可以改善手动性能。增强运动功能的另一种无痛的新兴技术是经颅直流刺激（TDC），可无创地增强大脑兴奋性。大多数改善中风运动功能的神经调节研究都集中在轻度手运动障碍的患者上。该赠款提案将通过使用一种新颖的方法来治疗中风后慢性阶段中度至重度无力的患者，基于R-21的结果，几乎没有普遍接受的选择来减少手部残疾。在这些患者中，以功能电刺激（FES）形式传递到肌肉的电流可以帮助运动性能和运动训练。我们将将FES，PSS和TDC结合在创新的策略中。该赠款的第一个目的是比较单独的FES与单独的TDC，仅PSS，TDCS + PNS或SHAM TDCS + SHAM PSS密切相关的效果，对中风后慢性相中的上肢无力中度至重度无力的患者的运动障碍。第二个目的是根据AIM 1的结果比较最强大的神经调节干预措施的几次会议的影响，以及安慰剂（Sham PSS/TDC）与FES +特定任务特异性培训的影响，对执行日常生活活动的能力。在AIM 2中，干预措施将在六周的时间内对两组中度至重度无力无力的成人中风患者进行。拟议的范式代表了通过多学科链接打破转化研究中障碍的一步。 P.I.，Conforto博士，巴西神经刺激实验室的负责人，中等收入国家（MIC）机构，将与高收入国家（HIC）机构的研究人员合作：Leonardo Cohen博士，一位著名的研究人员，著名的研究人员，领导人类的皮质生理学和Stroke Rebabloke Rebabilitation Cartects Intamal Ninds； Case Western Reserve University的生物医学工程教授P. Hunter Peckham博士是FES的杰出研究员兼先驱。克利夫兰诊所神经外科手术系神经恢复中心的主任安德烈·马卡多（Andre Machado）博士，他在神经调节方案方面拥有丰富的经验。麦克风与HIC机构之间的合作将为促进有关非侵入性皮质神经调节和生物医学工程的研究奠定了基础，以成熟中风康复的策略。麦克风机构提供设备和设施，可为此提案提供全力支持。